The band and label postponed the release of their follow-up to Comalies, Karmacode, to early 2006. According to the band's website, this made it possible for more time to be spent on production, and to avoid the crowded summer 2005 release schedule for metal albums. On December 23, 2005 the band announced on their web site that all recording, mixing, and mastering on Karmacode had been completed. It was then announced that Karmacode would be released in the USA on April 4, 2006.
During their 2005 European Tour, Lacuna Coil performed two new songs (working titles "A2" and "Antonio") at selected concerts. "Our Truth" was referred to at the time as "Antonio". "A2" was re-named "Fragile", which is the opening track on Karmacode.
Karmacode debuted at #28 on the Billboard Charts. It was acclaimed by music critics and magazines. Corresponding with the release of the new album, Lacuna Coil toured with Rob Zombie throughout North America in early 2006, it also appeared at Ozzfest 2006 on the main stage. The band also played at the 2006 Download Festival (a three-day music festival in England's Donington Park), which was headlined by Metallica, Tool, and Guns N' Roses. It also played one night in the U.K. at Sheffield Corporation on October 17, 2006. That December, Lacuna Coil teamed up with In Flames, The Sword and Seemless for a U.S. Tour, as well as The Blackest of the Black 2006 Tour (with headlining act Danzig, and bands likeAsesino, Belphegor, and The Haunted).
Four singles were officially released from Karmacode: "Our Truth", "Closer", "Within Me", and a cover of Depeche Mode's "Enjoy the Silence." "Our Truth" was the first single released, and had a music video produced for it. The single peaked in the top forty on the U.S. Mainstream Rock charts.
In March 2007, Lacuna Coil joined Stone Sour and Shadows Fall on the Jägermeister Music Tour. In May, it toured the USA with Within Temptation and The Gathering, on the The Hottest Chicks in Metal Tour 2007. Departing from the official tour dates, the band stopped in Raleigh, North Carolina in early April to play with local bands Wounded Soul, Blatant Disarray, and Shadows Fall. It again departed from the tour schedule in Albuquerque, New Mexico in late April to play the Sunshine Theater with Stolen Babies, Beneath the Sky, and Shadows Fall.
In October 2007 Lacuna Coil played for the first time in Japan, during the Loudpark Festival '07 in Saitama City's Saitama Super Arena. In November 2007 they joined Megadeth, DevilDriver,Static-X and Bring Me the Horizon for the Australian leg of Megadeth's Gigantour.
